Orofacial clefts are a major public health problem, affecting one in every 500-1000 births worldwide. There has been substantial recent progress by our group and others in identifying genetic loci for cleft lip with or without cleft palate (CUP), confirming the suspected complexity in the genetic etiology of CUP. As the genetic factors contributing to CL/P emerge, it is essential to identify the phenotypic characteristics attributable to each gene in order to translate the emerging research results into clinical practice. The primary goal of this study is to identify the phenotypes that are segregating at a genetic level in cleft' families, thereby extending the clinical phenotypic spectrum of CUP and identifying apparently unaffected individuals who are likely to be carrying cleft genes (e.g. individuals with sub-clinical phenotypic expression). Upon meeting this goal, recurrence risk calculation and genetic counseling for this common birth defect will be vastly improved. The specific features that will be investigated include: handedness, craniofacial measurements, asymmetry (based on dermatoglyphic patterns and craniofacial measurements), velopharyngeal competence (by perceptual screening) and anatomy of the orbicularis oris muscle. In order to succeed in characterizing the individual genes involved in each CL/P phenotype, large numbers of families are necessary for statistical power. Therefore, the current grant proposal is an international planning grant with the aim of ascertaining the large numbers of families necessary for the study aims. Three populations are targeted: Guatemala, Spain, and Hungary, with preliminary contacts made for each population. During the two years of the planning grant, we will confirm the necessary collaborations and logistics for carrying out the research protocol in each study population, will have planning meetings at the University of Pittsburgh, will carry out a minimum of one trip to each population in order to collect pilot data, will have planning meetings at the University of Pittsburgh, will use the pilot data to develop the research plan (e.g. power studies and sample size targets, research protocol and instruments), and will prepare the final research plan and submit a grant proposal to carry out the research project. [unreadable] [unreadable] [unreadable]